title: Post-proteasomal and proteasome-independent generation of MHC class I ligands.
abstract: Peptide ligands presented by MHC class I molecules are produced by intracellular proteolysis, which often involves multiple steps. Initial antigen degradation seems to rely almost invariably on the proteasome, although tripeptidyl peptidase II (TPP II) and insulin-degrading enzyme (IDE) may be able to substitute for the proteasome in rare cases. Recent evidence suggests that the net effect of cytosolic aminopeptidases is destruction of potential class I ligands, although a positive role in selected cases has been documented. This may apply particularly to the trimming of long precursors by TPP II. In contrast, trimming of ligand precursors in the endoplasmic reticulum is essential for the generation of suitable peptides and has a substantial impact on the repertoire of ligands presented. Trimming by the ER aminopeptidase (ERAP) enzymes most likely acts on free precursors and is adapted to the needs of class I molecules by way of a molecular ruler mechanism. Trimming by ERAP enzymes also occurs for cross-presented ligands, which can alternatively be processed in a special endosomal compartment by insulin-regulated aminopeptidase.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité 1013, Paris 75015, France. peter.van-endert@inserm.fr
authors.forename: Peter
authors.initials: P
authors.lastname: van Endert
mesh_terms: D000626:Aminopeptidases / Q000276:immunology; D000818:Animals; D017951:Antigen Presentation / Q000276:immunology; D015551:Autoimmunity; D045142:Cross-Priming / Q000276:immunology; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / Q000276:immunology; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007339:Insulysin / Q000276:immunology; D008024:Ligands; D051379:Mice; D009369:Neoplasms / Q000276:immunology; D010455:Peptides / Q000276:immunology; D046988:Proteasome Endopeptidase Complex / Q000276:immunology*; D012697:Serine Endopeptidases / Q000276:immunology; D014777:Virus Diseases / Q000276:immunology
chemical_list: D015395:Histocompatibility Antigens Class I; D008024:Ligands; D010455:Peptides; D000626:Aminopeptidases; D004152:Dipeptidyl-Peptidases and Tripeptidyl-Peptidases; C048001:tripeptidyl-peptidase 2; D012697:Serine Endopeptidases; D007339:Insulysin; D046988:Proteasome Endopeptidase Complex